29.1 Introduction:

Cystic Fibrosis is an autosomal recessive genetic disorder which impairs the lungs, pancreas, liver and intestine. The disease leads to congestion of lungs due to thick viscous secretion, which takes place as a result of abnormal transport of chloride and sodium across the epithelium. Symptoms of cystic fibrosis often appear in early childhood or during infancy, such as bowel obstruction due to meconium ileus in newborn babies. Exercise is essential for growing children suffering with cystic fibrosis, to release mucus from the alveoli.

The major signs and symptoms of cystic fibrosis include:

• •  Difficulty in breathing (due to tracheal and lung congestion).

•  Accumulation of thick, sticky mucus.

•  Frequent lung infections (treated with antibiotics and other medications).

•  Sinus infections.

•  Despite a normal food intake the growth and weight gain is poor.

•  Infertility (males can be infertile due to congenital absence of the vas deferens).

•  Salty tasting skin.

•  Coughing or shortness of breath.

29.2 Cystic fibrosis transmembrane conductance regulator gene:

• •  Cystic fibrosis is caused by the mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene found at the q31.2 locus of chromosome 7.

•  CFTR gene is relatively large around 230,000 base pairs long and produces a 1,480 amino acid long protein. CFTR protein is a membrane bound glycoprotein with a molecular mass of 170 kDa.

•  Different mutations in the CFTR gene is the major cause of cystic fibrosis, one such mutation is due to the deletion of three nucleotides which corresponds to the amino acid phenylalanine (F) located at the 508 th position on the protein. This mutation is denoted by ΔF508 (Δ signifies deletion, F is phenylalanine, 508 is the position of amino acid) and accounts for 66-70% cystic fibrosis cases worldwide.

•  Normal people have one or two working copies (alleles) of the CFTR gene, only one is needed to prevent cystic fibrosis. Cystic fibrosis develops in individuals who cannot produce a functional CFTR protein. CFTR gene is structurally similar to ATP-binding cassette transporters (ABC) gene and the product of CFTR gene is a CFTR protein.